Design, synthesis and antimalarial activity of novel, quinoline-Based, zinc metallo-aminopeptidase inhibitors

PfA-M1, a neutral zinc aminopeptidase of Plasmodium falciparum, is a new potential target for the discovery of antimalarials. The design and synthesis of a library of 45 quinoline-based inhibitors of PfA-M1 is reported. The best inhibitor displays an IC50 of 854 nM. The antimalarial activity on a CQ-resistant strain and the specificity towards mammalian aminopeptidase N are also discussed.